The effect of solvation by water molecules on the nucleophilicity of the superoxide anion, O2(•-), has been investigated in detail by mass spectrometric experiments and quantum chemical calculations, including direct dynamics trajectory calculations. Specifically, the SN2 reactions of O2(•-)(H2O)n clusters (n = 0-5) with CH3Cl and CH3Br were studied. It was found that the reaction rate decreases when the number of water molecules in the cluster increases; furthermore, reaction with CH3Br is in general faster than reaction with CH3Cl for clusters of the same size. In addition, key transition-state geometries were identified and probed by Born-Oppenheimer molecular dynamics, showing how a water molecule may be transferred from the nucleophile to the leaving group during the reaction. The computational models are in good agreement with the experimental observations.